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Introduction: Myelodysplastic syndromes (MDS) are characterized by bone marrow failure, peripheral blood cytopenias and a high risk of progression to acute myeloid leukemia (AML), which is associated with a poor prognosis and low survival rates. This study combined surveys with patient chart reviews to document real-world clinical practice and burden of MDS, including perspectives of physicians, patients and caregivers and underlying discrepancies. Methods: Physicians in major European countries and the US provided information on 1445 patients, stratified into lower- (LR) and higher-risk (HR) MDS. Patients had the opportunity to complete questionnaires describing the impact of MDS. Caregivers had the option to report on the burden of caring for a patient with MDS. Results: While supportive treatment was common, mainly with erythropoietins (52%), anti-AML agents were more frequently used in HR than in LR patients (70% vs 20%), while HR patients generally received more transfusions (48% vs 36%). Symptoms with the largest discordance between patient vs physician reporting were excessive bruising (30% vs 14%), GI side effects (19% vs 6%) and feeling tired or fatigued (68% vs 56%). A bigger impact of fatigue was reported on the European Organization for the Research and Treatment of Cancer Quality of Life questionnaire (EORTC QLQ-C30) for HR vs LR patients (43.2 vs 36.5 on a scale from 0 to 100). There was discordance between caregivers vs physicians on reporting of weekly caregiver hours (45.4 vs 29.2) with a Zarit Burden Interview score (ZBI, score 0–88) of 25.4. Conclusions: Patients reported a higher frequency than their physicians of top symptoms, with MDS-related disruptions in daily life for both patients and caregivers. There is a need for new therapeutic strategies, along with shared understanding and decision making among patients, caregivers and physicians, to optimize disease management and improve quality of life in people living with MDS. [ABSTRACT FROM AUTHOR]

Many pre-transplant factors are known to influence the outcome of allogeneic stem cell transplantation (SCT) treatment in myelodysplastic syndromes (MDS). However, patient cohorts are often heterogeneous by disease stage and treatment modalities, which complicates interpretation of the results. This study aimed to obtain a homogeneous patient cohort by including only de novo MDS patients who received upfront allogeneic SCT after standard high dose myelo-ablative conditioning. The effect of pre-transplant factors such as age, disease stage, transfusions, iron parameters and comorbidity on overall survival (OS), non-relapse mortality (NRM), and relapse incidence (RI) was evaluated in 201 patients. In this cohort, characterized by low comorbidity and a short interval between diagnosis and transplantation, NRM was the most determinant factor for survival after SCT (47 % after 2-year follow-up). WHO classification and transfusion burden were the only modalities with a significant impact on overall survival after SCT. Estimated hazard ratios (HR) showed a strongly increased risk of death, NRM and RI, in patients with a high transfusion-burden (HR 1.99; P = 0.006, HR of 1.89; P = 0.03 and HR 2.67; P = 0.03). The HR's for ferritin level and comorbidity were not significantly increased. [ABSTRACT FROM AUTHOR]

Background: Hypomethylating drugs are the standard treatment for patients with high-risk myelodysplastic syndromes. Survival is poor after failure of these drugs; there is no approved second-line therapy. We compared the overall survival of patients receiving rigosertib and best supportive care with that of patients receiving best supportive care only in patients with myelodysplastic syndromes with excess blasts after failure of azacitidine or decitabine treatment.Methods: We did this randomised controlled trial at 74 hospitals and university medical centres in the USA and Europe. We enrolled patients with diagnosis of refractory anaemia with excess blasts (RAEB)-1, RAEB-2, RAEB-t, or chronic myelomonocytic leukaemia based on local site assessment, and treatment failure with a hypomethylating drug in the past 2 years. Patients were randomly assigned (2:1) to receive rigosertib 1800 mg per 24 h via 72-h continuous intravenous infusion administered every other week or best supportive care with or without low-dose cytarabine. Randomisation was stratified by pretreatment bone marrow blast percentage. Neither patients nor investigators were masked to treatment assignment. The primary outcome was overall survival in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT01241500.Findings: From Dec 13, 2010, to Aug 15, 2013, we enrolled 299 patients: 199 assigned to rigosertib, 100 assigned to best supportive care. Median follow-up was 19·5 months (IQR 11·9-27·3). As of Feb 1, 2014, median overall survival was 8·2 months (95% CI 6·1-10·1) in the rigosertib group and 5·9 months (4·1-9·3) in the best supportive care group (hazard ratio 0·87, 95% CI 0·67-1·14; p=0·33). The most common grade 3 or higher adverse events were anaemia (34 [18%] of 184 patients in the rigosertib group vs seven [8%] of 91 patients in the best supportive care group), thrombocytopenia (35 [19%] vs six [7%]), neutropenia (31 [17%] vs seven [8%]), febrile neutropenia (22 [12%] vs ten [11%]), and pneumonia (22 [12%] vs ten [11%]). 41 (22%) of 184 patients in the rigosertib group and 30 (33%) of 91 patients in the best supportive care group died due to adverse events and three deaths were attributed to rigosertib treatment.Interpretation: Rigosertib did not significantly improve overall survival compared with best supportive care. A randomised phase 3 trial of rigosertib (NCT 02562443) is underway in specific subgroups of patients deemed to be at high risk, including patients with very high risk per the Revised International Prognostic Scoring System criteria.Funding: Onconova Therapeutics, Leukemia & Lymphoma Society. [ABSTRACT FROM AUTHOR]

This article discusses the use of the epigenetic drug, VIDAZA, in the treatment of myelodysplastic syndromes (MDS). According to the article, approvals from the U.S. Food and Drug Administration (FDA) and the European Regulatory Authority for the drug signal an encouraging step in the treatment of the bone marrow disorder. It highlights a study which shows that a non-transplant medical therapy can significantly extend survival for patients with higher-risk form of MDS.